product name Odanacatib (MK-0822)
Description: Odanacatib, also known as MK-0822, is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with IC50 of 0.2 nM/1 nM, and demonstrated high selectivity versus off-target cathepsin B, L, S. Odanacatib selectively binds to and inhibits the activity of cathepsin K, which may result in a reduction in bone resorption, improvement of bone mineral density, and a reversal in osteoporotic changes. Currently, Odanacatib is undergoing evaluation for fracture risk reduction in a phase III trial with ＞16000 patients with postmenopausal osteoporosis.
References: Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8; J Bone Miner Res. 2011 Feb;26(2):252-62
525.56
Formula
C25H27F4N3O3S
CAS No.
603139-19-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (190.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
4% DMSO+corn oil: 5 mg/mL
Synonyms
MK-0822
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19409555
| In Vitro |
In vitro activity: In vitro, Odanacatib shows the high inhibitory activity and selectivity on cathepsin K with IC50 values of 0.2 nM and 1 nM for human cathepsin K and rabbit cathepsin K, respectively. Furthermore, Odanacatib also shows similar potencies in whole human cell enzyme occupancy assays with corrected IC50 of 5 nM. A recent study shows that Odanacatib results in reduction of Osteoclast (OC) resorption activity by interrupting intracellular vesicular trafficking Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In preclinical rats, Odanacatib (10 mg/kg) exhibits excellent pharmacokinetics with clearance (Cl: 2 mL kg-1 min-1), low volume of distribution (Vdss: 1.1 L kg-1), half-life (T1/2: 6 hours) and oral bioavailability (F: 8%), respectively. Besides, Odanacatib also exhibits excellent metabolic stability in rat hepatocytes with a 96% recovery of the parent identity. Odanacatib (ODN) administrated by p.o. prevents bone loss in ovariectomized (OVX) rabbits in a dose-related manner. Moreover, Odanacatib (9 µM/day) leads to a significant increase in proximal femur bone mineral density (BMD) (7.8%), femoral neck BMD (10.8%) and the greater trochanter BMD (6.5%). In the estrogen-deficient, skeletally mature rhesus monkeys, long-term treatment with Odanacatib effectively inhibits bone turnover without reducing osteoclast number and maintains normal biomechanical properties of the spine of OVX nonhuman primates. |
| Animal model | Ovariectomized (OVX) rabbit model |
| Formulation & Dosage | Formulated in diet; ≤9 µM/day; Oral gavage |
| References | Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8; J Bone Miner Res. 2011 Feb;26(2):252-62 |
